Editor's Note: Neurobiologist Larry Young studies a monogamous species of rodent, the prairie vole, to understand the behavior and chemistry behind relationships. In The Chemistry between Us, Young teams up with science journalist Brian Alexander to describe science's progress in illuminating the neurochemistry behind our experience of love. In this excerpt, the authors describe the work of neurobiologist Oliver Bosch, a specialist in maternal behavior, who worked with Young's prairie voles to study the bitter price of bonding.

To investigate the rodent version of getting hugs, and what happens in the absence of hugs from a bonded partner, Bosch took virgin males and set them up in vole apartments with roommates—either a brother they hadn't seen in a long time or an unfamiliar virgin female. As males and females are wont to do, the boy-girl roommates mated and formed a bond. After five days, he split up half the brother pairs, and half the male-female pairs, creating what amounted to involuntary vole divorce. Then he put the voles through a series of behavioral tests.

The first is called the forced-swim test. Bosch likens it to an old Bavarian proverb about two mice who fall into a bucket of milk. One mouse does nothing and drowns. The other tries to swim so furiously the milk turns into butter and the mouse escapes. Paddling is typically what rodents will do if they find themselves in water; they'll swim like crazy because they think they'll drown if they don't. (Actually, they'll float but apparently no rodent floaters have ever returned to fill in the rest of the tribe.)

The voles that were separated from their brothers paddled manically. So did the voles who stayed with their brothers and the voles who stayed with their female mates. Only the males who'd gone through vole divorce floated listlessly as if they didn't care whether they drowned.

"It was amazing," Bosch recalls. "For minutes, they would just float. You can watch the video and without knowing which group they were in, you can easily tell if it's an animal separated from their partner, or still with their partner." Watching the videos of them bob limply, it's easy to imagine them moaning out "Ain't No Sunshine When She's Gone" with their tiny vole voices.

Next Bosch subjected the voles to a tail-suspension test. This test uses the highly sophisticated technique of duct taping the end of an animal's tail to a stick and suspending it. As in the swim test, a rodent thus suspended will usually flail and spin his legs like a cartoon character who's run off the edge of a cliff. Once again, though, while the other males did just that, the divorced males hung like wet laundry.

In a final behavior test, Bosch placed the voles on an elevated maze, like the ones we've already described that tested anxiety. On such a maze, the animal's desire to investigate fights with its fear of exposed areas. Compared to the other voles, the divorced males were significantly less likely to explore the open arms of the maze.

All these tests, commonly used to test lab animals for depression, showed that if you separate a pair-bonded male vole from his mate, you'll get a very mopey vole who uses what's called passive-stress coping to deal with the overwhelming anxiety of partner loss. "When the separation takes place, this is what causes the animals to feel so bad," Bosch explains. "We found this increased depressive behavior and that tells us the animal is not feeling well." He doesn't mean "under the weather," he means the divorced voles are emotionally miserable. "It is like when my wife went to the States for a post-doc for one year, so I knew I wouldn't see her for at least six months. Well, I was sitting at home, laying on the couch, not motivated to do anything, not to go out and meet friends like I usually would."

Koob and others have used drugs to create the very same behavior in other lab animals. When the drugs are taken away from rats and mice, they display the same passive responses to elevated mazes. They withdraw socially. They mope. Human addicts do the same, Koob points out, mentioning characters in movies like Leaving Las Vegas and Trainspotting as examples.

To explain the physiology behind this passive depression state in the separated voles, Bosch checked their chemistry. The males separated from their mates had much higher levels of corticosterone, a stress chemical, in their blood than did any of the other groups, including voles separated from their brothers. Their HPA axis was working so hard, their adrenal glands weighed more. Bosch nailed CRF's role in driving both the HPA axis overdrive and the mopey behavior by blocking CRF receptors in the voles' brains. When he did, the divorced voles no longer hung limply from the sticks. They didn't float for as long in the water. They still remembered their mates, and were still bonded to them; they just didn't worry about it when they left them.

But here's the strange thing: both the voles who stayed with their female mates and the voles who were forced to split from the females had much more CRF in the BNST than did males who lived with, or were separated from, their brothers. In other words, loads of this stress-related hormone were being pumped in both the voles who got depressed after separation and voles who were still happily bonded and didn't show signs of passive-stress coping.

"Bonding itself produces high CRF," Bosch says. "But this does not mean the system is also firing." There is something fundamental about living with a mate that results in more CRF stress hormone in the brain, but that also prevents the engagement of the HPA stress axis as long as the mates stay together. Using an interesting metaphor for bonding, Bosch says "I compare it to a rifle. As soon as they form a pair-bond, the rifle is loaded with a bullet. But the trigger isn't pulled unless there is separation." He thinks that vasopressin serves as the chemical trigger to fire off the HPA axis during separation, though the exact roles of both oxytocin and vasopressin are still unclear.